The Food and Drug Administration (FDA) approved Erleada (apalutamide) for the treatment of patients who have nonmetastatic castration-resistant prostate cancer (CRPC). The drug is now the first FDA-approved treatment in this setting.

The approval is based on the phase 3 SPARTAN trial in which Erleada reduced the risk of metastasis or death by 72 percent in patients with nonmetastatic CRPC. The median metastasis-free survival (MFS) was 40.5 months in the Erleada arm versus 16.2 months in the placebo arm.

“The FDA evaluates a variety of methods that measure a drug’s effect, called endpoints, in the approval of oncology drugs. This approval is the first to use the endpoint of metastasis-free survival, measuring the length of time that tumors did not spread to other parts of the body or that death occurred after starting treatment,” Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “In the trial supporting approval, Erleada had a robust effect on this endpoint. This demonstrates the agency’s commitment to using novel endpoints to expedite important therapies to the American public."

The SPARTAN trial evaluated the safety and efficacy of Erleada versus placebo in 1,207 patients with nonmetastatic CRPC and a rapidly rising prostate specific antigen (PSA) level despite receiving continuous androgen deprivation therapy. Nonmetastatic status was determined by a negative bone scan, as well as a negative CT of the pelvis, abdomen, chest and brain.

Patients were required to have a PSA doubling time of 10 months or shorter, since “prior data has shown that these are the patients most at risk for developing metastases and death,” said Small.

Patients were randomized in a 2-1 ratio to 240 mg of Erleada daily (806 patients) or placebo (401 patients). The average baseline PSA doubling time was less than five months in both arms. Patients who developed metastases were allowed to receive Zytiga (abiraterone acetate) plus prednisone, which Small noted is the standard of care in patients with metastatic CRPC.

Beyond the primary MFS endpoint, secondary endpoints included time to metastasis, progression-free survival, time to symptomatic progression and overall survival (OS). For patients who developed metastases, the researchers also evaluated the time between randomization to first treatment for metastatic CRPC and subsequent progression (PFS2).

At a median follow-up of 20.3 months, 61 percent of the Erleada arm remained on treatment compared with 30 percent of the placebo group. An interim OS analysis (24 percent of events) revealed a trend favoring Erleada.

Adverse events led to discontinuation in 10.7 percent and 6.3 percent of the Erleada and control arms, respectively. Neither group had a reduction in mean baseline health-related quality-of-life scores as the trial progressed, and there was no difference over time in the scores between the groups.

Eighty percent of placebo patients who progressed and 56 percent of Erleada patients were treated for metastatic CRPC. The researchers noted that PFS2 was longer for patients who were initially randomized to Erleada.

“There is a population of men with prostate cancer who have no visible evidence of spread but who have a rise in their blood markers. These patients can have a poor prognosis, and until now, the optimal management of their cancer remained an enigma. These findings suggest there may finally be a treatment that holds real promise for extending their health and their lives,” presscast moderator and ASCO expert Sumanta K. Pal, M.D., a medical oncologist and assistant clinical professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, said in a statement, when the SPARTAN data were presented at the 2018 Genitourinary Cancers Symposium.